Managing erectile dysfunction in patients treated with beta-blockers

I read this article (Beta-blockers for cardiovascular conditions: one size does not fit all patients)
hoping to find the answer to my older male patient’s problem with beta-blockers and erectile dysfunction.
Time and time again they come out of hospital post-MI on metoprolol and the ability to maintain an erection
seems to have been left at the hospital. Over the last few weeks I have spoken to one of the cardiologists who
suggested switching those who need to stay on a beta-blocker to carvedilol as it is more cardioselective...but reading your article
this doesn't seem to be the case. I wonder if you can comment on what you would do with these men both in the situation of preserved
ejection fraction and those with reduced ejection fraction. The quality of life for them is dreadful when they can no longer perform.
It has huge psychological burden and makes compliance tricky too. The other piece of advice my friendly cardiologist gave me was post-MI,
if they can walk up two flights of stairs Viagra was fine; again, not what I had been led to believe historically.

Dr Louise Kuegler

Response from the bpacnz editorial team:

The management of erectile dysfunction in patients taking beta-blockers is complicated by the possibility of overlapping causes. Erectile dysfunction shares a number of risk
factors with coronary artery disease, and has been proposed as a marker for cardiovascular disease.1 One small study found that following discharge from hospital post-myocardial
infarction, 84% of male patients reported that they had pre-existing erectile dysfunction.2 Erectile dysfunction is reported in studies of patients taking a range of beta-blockers,
including carvedilol, and therefore it is considered to be a class-wide adverse effect.3–5 Awareness of the possibility of sexual dysfunction with the use of beta-blockers may
also contribute to erectile dysfunction via a nocebo effect (the opposite of placebo effect).6

Optimisation of cardiovascular treatment should be the first consideration post-myocardial infarction, in patients with or without heart failure.
Withdrawal of the beta-blocker is likely to be the most effective way to alleviate beta-blocker-related erectile dysfunction. However, this will only
be appropriate from six months post-myocardial infarction if re-vascularisation has occurred and patients do not have another indication for a beta-blocker,
such as atrial fibrillation or heart failure.

Will switching from metoprolol to carvedilol improve the patient’s symptoms?

The recommendation to switch patients with erectile dysfunction who require ongoing beta-blocker treatment to carvedilol is based
on pharmacological theory. Unfortunately, the theory is not supported by evidence.

Carvedilol* is classified as a vasodilating beta-blocker as it reduces peripheral resistance by binding to alpha-adrenoceptors without
affecting cardiac output.4 Additionally, carvedilol can produce vasodilation by increasing nitric oxide (NO) production.4 NO-dependent
relaxation of the cavernosal smooth muscles is a critical step in the development of an erection.3

There is only one study that we are aware of that has examined the effect of carvedilol on sexual activity. Investigators found that in a group of 160 males
(without a history of cardiovascular events), aged 40 to 49 years, who had been recently diagnosed with hypertension, carvedilol was associated with 15 reports
of erectile dysfunction over a 16 week period, compared to one report of erectile dysfunction in patients taking valsartan (an angiotensin II receptor antagonist).7

Erectile dysfunction is thought to be a class-wide adverse effect associated with all the beta-blockers available in New Zealand. Therefore, it is
unlikely that choosing a different type of beta-blocker, i.e. cardioselective or non-selective, will make a clinical difference to patients with sexual
dysfunction. However, as there appears to be a nocebo affect associated with the use of beta-blockers the act of switching a patient with erectile
dysfunction from metoprolol to carvedilol, may produce therapeutic benefit.

*N.B. Carvedilol is not a cardioselective beta-blocker as it binds to alpha1, beta1 and beta2-adrenoceptors. Atenolol,
bisoprolol and metoprolol are cardioselective as they have a greater affinity for beta1-adrenoceptors which are predominantly located in the heart.

When are phosphodiesterase-5 inhibitors appropriate in patients with cardiovascular disease?

Patients with beta-blocker related erectile dysfunction may request a prescription for sildenafil. A recent history of
myocardial infarction is a contraindication to the use of sildenafil, however, the manufacturers do not specify a time
period.8 A measure such as being able to walk up two flights of stairs post-myocardial infarction without chest
pain suggests that a patient has recovered to some degree and that sexual activity is likely to be safe. However, there
are a number of other factors that would need to be considered such as the potential for medicine interactions, e.g. the
concurrent use of nitrates or alpha blockers, the overall health of the patient and the amount of time since the cardiac
event. Guidelines from the United Kingdom recommend avoiding sildenafil in the first 90 days following a myocardial infarction.9

In general, patients with heart failure and erectile dysfunction can be successfully treated with PDE5-inhibitors and this may even correlate with an increase in exercise
tolerance.1 There is no specific guidance on the treatment of erectile dysfunction in patients with heart failure with preserved ejection fraction (HF-PEF). It would seem
reasonable to manage these patients in the same way as those with heart failure with reduced ejection fraction (HF-REF), while noting that patients with HF-PEF may
be more “brittle”. A lower threshold for withholding treatment with a PDE5-inhibitor due to cardiovascular instability is therefore recommended and discussion with
a cardiologist is advised if there are concerns.

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